Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. Studies of emotional learning in the amygdala have identified many of the neural circuits and mechanisms involved in normal fear and anxiety, and have suggested ways in which alterations in these mechanisms can provoke anxiety disorders. However, much more needs to be learned about these circuits before more effective treatments can be developed. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar circuits involved in emotion, including emotional learning. In the present project we focus on the synaptic organization of inputs from three transmitter-specific neuromodulatory systems of the brainstem and basal forebrain. These include noradrenergic and dopaminergic systems of the brainstem, as well as the cholinergic/GABAergic inputs from the basal forebrain. Despite the importance of these systems for the physiology and pathophysiology of amygdalar emotional function, there have been few studies of these circuits using state-of-the-art multiple- labeling light and electron microscopic methods. Specific Aim #1 will analyze the innervation of the BLC by cholinergic and GABAergic neurons of the basal forebrain. Specific Aim #2 will study the Innervation of pyramidal cells and distinct interneuronal subpopulations by noradrenergic inputs to the BLC. Specific Aim #3 will examine the dopaminergic innervation of the BLC, and its interactions with dopamine receptors and glutamatergic sensory inputs from the temporal cortex. The overarching hypothesis of this research is that there is a parcellation of emotional mnemonic subfunctions subserved by separate neuromodulatory systems projecting to the BLC, and that this will involve the differential targeting of discrete neuronal subpopulations and compartments by different neuromodulatory systems, and by the expression of different receptor subtypes in distinct neuronal subpopulations. Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotion.

Public Health Relevance

Anxiety disorders, including post-traumatic stress disorder (PTSD), affect about 40 million American adults each year (18% of the population) and thus represent a major health problem. The main brain system involved in fear and anxiety is the amygdala, including its connections with discrete forebrain and brainstem regions. The proposed study is the continuation of a long-term investigation of the synaptic organization of the basolateral nuclear complex of the rat amygdala (BLC) whose main goal is to elucidate the basic chemical neuroanatomy of amygdalar systems involved in emotion.